scholarly journals Simian Varicella Virus DNA in Saliva and Buccal Cells After Experimental Acute Infection in Rhesus Macaques

2019 ◽  
Vol 10 ◽  
Author(s):  
Vicki Traina-Dorge ◽  
Satish Mehta ◽  
Bridgette Rooney ◽  
Brian Crucian ◽  
Lara Doyle-Meyers ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Acute Infection ◽  
Buccal Cells ◽  
Simian Varicella Virus ◽  
Varicella Virus

scholarly journals Robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques

2014 ◽  
Vol 20 (5) ◽  
pp. 526-530 ◽  
Author(s):  
Vicki Traina-Dorge ◽  
Robert Sanford ◽  
Stephanie James ◽  
Lara A. Doyle-Meyers ◽  
Eileen de Haro ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Rhesus Macaques ◽  
Simian Varicella Virus ◽  
Varicella Virus ◽  
Anti Inflammatory

scholarly journals The ORF61 Protein Encoded by Simian Varicella Virus and Varicella-Zoster Virus Inhibits NF-κB Signaling by Interfering with IκBα Degradation

2015 ◽  
Vol 89 (17) ◽  
pp. 8687-8700 ◽  
Author(s):  
Travis Whitmer ◽  
Daniel Malouli ◽  
Luke S. Uebelhoer ◽  
Victor R. DeFilippis ◽  
Klaus Früh ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Varicella Zoster Virus ◽  
Primary Infection ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus

ABSTRACTVaricella-zoster virus (VZV) causes chickenpox upon primary infection and establishes latency in ganglia. Reactivation from latency causes herpes zoster, which may be complicated by postherpetic neuralgia. Innate immunity mediated by interferon and proinflammatory cytokines represents the first line of immune defense upon infection and reactivation. VZV is known to interfere with multiple innate immune signaling pathways, including the central transcription factor NF-κB. However, the role of these inhibitory mechanismsin vivois unknown. Simian varicella virus (SVV) infection of rhesus macaques recapitulates key aspects of VZV pathogenesis, and this model thus permits examination of the role of immune evasion mechanismsin vivo. Here, we compare SVV and VZV with respect to interference with NF-κB activation. We demonstrate that both viruses prevent ubiquitination of the NF-κB inhibitor IκBα, whereas SVV additionally prevents IκBα phosphorylation. We show that the ORF61 proteins of VZV and SVV are sufficient to prevent IκBα ubiquitination upon ectopic expression. We further demonstrate that SVV ORF61 interacts with β-TrCP, a subunit of the SCF ubiquitin ligase complex that mediates the degradation of IκBα. This interaction seems to inactivate SCF-mediated protein degradation in general, since the unrelated β-TrCP target Snail is also stabilized by ORF61. In addition to ORF61, SVV seems to encode additional inhibitors of the NF-κB pathway, since SVV with ORF61 deleted still prevented IκBα phosphorylation and degradation. Taken together, our data demonstrate that SVV interferes with tumor necrosis factor alpha (TNF-α)-induced NF-κB activation at multiple levels, which is consistent with the importance of these countermechanisms for varicella virus infection.IMPORTANCEThe role of innate immunity during the establishment of primary infection, latency, and reactivation by varicella-zoster virus (VZV) is incompletely understood. Since infection of rhesus macaques by simian varicella virus (SVV) is used as an animal model of VZV infection, we characterized the molecular mechanism by which SVV interferes with innate immune activation. Specifically, we studied how SVV prevents activation of the transcription factor NF-κB, a central factor in eliciting proinflammatory responses. The identification of molecular mechanisms that counteract innate immunity might ultimately lead to better vaccines and treatments for VZV, since overcoming these mechanisms, either by small-molecule inhibition or by genetic modification of vaccine strains, is expected to reduce the pathogenic potential of VZV. Moreover, using SVV infection of rhesus macaques, it will be possible to study how increasing the vulnerability of varicella viruses to innate immunity will impact viral pathogenesis.

scholarly journals Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

2016 ◽  
Vol 90 (23) ◽  
pp. 10823-10843 ◽  
Author(s):  
Nicole Arnold ◽  
Thomas Girke ◽  
Suhas Sureshchandra ◽  
Ilhem Messaoudi
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Sensory Ganglia ◽  
Simian Varicella Virus ◽  
Varicella Virus

ABSTRACTPrimary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression.IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection.

scholarly journals Simian varicella virus gene expression during acute and latent infection of rhesus macaques

2011 ◽  
Vol 17 (6) ◽  
pp. 600-612 ◽  
Author(s):  
Christine Meyer ◽  
Amelia Kerns ◽  
Alex Barron ◽  
Craig Kreklywich ◽  
Daniel N. Streblow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Latent Infection ◽  
Rhesus Macaques ◽  
Simian Varicella Virus ◽  
Virus Gene ◽  
Varicella Virus ◽  
Virus Gene Expression

scholarly journals Simian varicella virus infection of Chinese rhesus macaques produces ganglionic infection in the absence of rash

2012 ◽  
Vol 18 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Werner J. D. Ouwendijk ◽  
Ravi Mahalingam ◽  
Vicki Traina-Dorge ◽  
Geert van Amerongen ◽  
Mary Wellish ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rhesus Macaques ◽  
Simian Varicella Virus ◽  
Varicella Virus ◽  
Chinese Rhesus Macaques

scholarly journals Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

2009 ◽  
Vol 5 (11) ◽  
pp. e1000657 ◽  
Author(s):  
Ilhem Messaoudi ◽  
Alexander Barron ◽  
Mary Wellish ◽  
Flora Engelmann ◽  
Alfred Legasse ◽  
...  
Keyword(s):  
Virus Infection ◽  
Varicella Zoster Virus ◽  
Rhesus Macaques ◽  
Varicella Zoster Virus Infection ◽  
Simian Varicella Virus ◽  
Varicella Zoster ◽  
Varicella Virus

scholarly journals Intrabronchial Infection of Rhesus Macaques with Simian Varicella Virus Results in a Robust Immune Response in the Lungs

2014 ◽  
Vol 88 (21) ◽  
pp. 12777-12792 ◽  
Author(s):  
K. Haberthur ◽  
C. Meyer ◽  
N. Arnold ◽  
F. Engelmann ◽  
D. R. Jeske ◽  
...  
Keyword(s):  
Immune Response ◽  
Rhesus Macaques ◽  
Simian Varicella Virus ◽  
Robust Immune Response ◽  
Varicella Virus
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